Intensive alternating immunochemotherapy protocol GMALL/B-ALL/NHL2002 is curative for more than 90% of PMBL patients and late toxicity in young patients is moderated. Second malignancies and late cardiotoxicity occurred in 2.4% and 2.4% of patients, respectively. Acute toxicity included pancytopenia grade 3/4, neutropenic fever, and treatment related mortality rate of 0.8%. Eight (6%) patients had recurrent/refractory disease, however, no central nervous system (CNS) relapse was observed. Positron emission tomography-computed tomography (PET-CT) results at the end of chemotherapy were predictive for outcome: OS and PFS at 5 year were 96% and 94% in PET-CT negative patients, respectively, and 70% and 70% in PET-CT-positive patients (p = 0.004 for OS, p = 0.01 for PFS).
Unfolder trial free#
With a median (range) follow up of 9 (1–17) years, 5-year overall survival (OS) and 5-year progression free survival (PFS) were 94% and 92%, respectively. A median (range) age of patients was 30 (18–59) years, and 60% were female. Majority of patients (77%) received consolidative radiotherapy. Here we present results of treatment of 124 patients with PMBL over a period between 20 with the use of a protocol designed for aggressive B-cell lymphoma GMALL/B-ALL/NHL2002 including 6 cycles of alternating immunochemotherapy with intermediate-dose methotrexate in each cycle, and reduced total doxorubicin dose (100 mg/m² for whole treatment). Treatment regimens frequently used include RCHOP ± radiotherapy, DAEPOCH-R, or occasionally more intensive protocols. Primary mediastinal B-cell lymphoma (PMBL) is currently curable in 85–95% of patients. Supported by Deutsche Krebshilfe, Amgen and Roche. Our results indicate a very favorable 3-year OS of 96% in PMBCL pts treated with R-CHOP.
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Testing RT in PET-positive residual tumors in a randomized trial can solve the question, while RT in PET-negative pts is studied in the ongoing randomized IELSG 37 trial. The results suggest a benefit of RT only for pts, who are responding to R-CHOP with PR. Pts assigned to RT had a superior EFS mostly due to a higher PR rate in the no-RT arm triggering RT, with no differences in PFS and OS. The results reveal no differences between R-CHOP-14 vs R-CHOP-21.
Unfolder trial series#
Conclusions: To our knowledge, this is the largest series of PMBCLs so far, which have been treated in a prospective, randomized trial in the rituximab era. Dose-densification of R-CHOP-21 by R-CHOP-14 did not improve EFS, PFS nor OS. In an as treated analysis the difference between the RT and the no-RT arm was not significant (p = 0.136). 78% p = 0.007), mostly due to events caused by initiation of RT (n = 5) in the no-RT arm. 3-year EFS was superior in pts assigned to RT (94% vs. Response RT vs no-RT were CR/Cru 94% vs 84%, PR 2% vs 10%, PD 2% vs 4%. 96% (79/82) received RT per protocol and 5 pts in the no-RT arm received unplanned RT (4 after PR and 1 after CR/CRu).
Results: 131 PMBCLs were included with a median age of 34 years, 54% were female, 79% had elevated LDH > UNV and 24% had E.
Response was evaluated by the Internat Standardized Response Criteria, Cheson 1999. Primary endpoint was event-free survival (EFS), secondary endpoints were progression-free (PFS) and overall survival (OS). Pts were randomized in a 2 x 2 factorial design to 6xR-CHOP-14 or 6x-R-CHOP-21 without RT or with RT (39.6 Gy) to Bulk and E. Methods: The UNFOLDER trial included 18-60 year-old pts (aaIPI = 0 with Bulk or aaIPI = 1) qualifying for radiotherapy to Bulk or extralymphatic involvement (E). Therapy is based on R-CHOP or similar regimens, but the role of treatment intensification and consolidative radiotherapy (RT) is controversial, because data from randomized trials are rare. Background: Primary mediastinal B-cell lymphoma (PMBCL) is a distinct entity of aggressive lymphoma, which typically presents in young patients (pts) with a bulky mediastinal mass.